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Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 289 records · Page 16Linked to original sources
PubMed1995

Spatiotemporal gait parameters measured using the Bessou gait analyzer in 79 healthy subjects. Influence of age, stature, and gender. Study Group on Disabilities due to Musculoskeletal Disorders (Groupe de Recherche sur le Handicap de l'Appareil Locomoteur, GRHAL).

The Bessou gait analyzer provides quantitative measurements of spatiotemporal gait parameters. The purpose of this study was to determine whether and how these parameters are influenced by age, stature, and gender. Seventy-nine normal individuals (38 males aged 20 to 80 years and 41 females aged 20 to 80 years) were divided into ten-year age groups. Males and females were studied separately. In each subject, the Bessou gait analyzer was used to measure spatiotemporal gait parameters (spatial parameters: stride and step lengths; temporal parameters: cycle, stance and swing durations). Mean walking speed was calculated in each subgroup. In both males and females, all study parameter values were identical for the left and right sides. Females younger than 60 years had shorter stride and step lengths (M: 1.5 +/- 0.2 m; F: 1.3 +/- 0.1; p < 0.001) but faster pace values (M: 104.8 +/- 9.0 cycles/min; F: 115.6 +/- 7.6 cycles/min; p < 0.001) than males, and consequently mean walking speed was similar in females and males (M: 4.8 km/h +/- 0.8 km/h; F: 4.4 km/h +/- 0.6 km/h). In contrast, females older than 60 years walked at the same pace as males and consequently had slower walking speeds. Stride length was correlated with age, stature, and gender. However, age was correlated with stature, and only age and gender had independent effects on gait parameters in the multiple regression analysis. In subjects of similar age and gender, effects of stature may need to be taken into account.

Adult↗
PubMed1995

Test time and efficiency of the dynamic strategy in glaucoma perimetry.

The dynamic strategy is a perimetric measurement procedure where by the luminance-step sizes are optimized according to physiological data. In contrast to the traditional 4- to 2-dB strategy, the step sizes are not constant but vary between 2 and 10 dB depending on the sensitivity. We examined 40 eyes of 40 glaucoma patients with both the traditional and the dynamic strategy using a modified Octopus 1-2-3 perimeter. A total of 16 visual field locations were examined using both strategies 3 times each in alternation. The order of the initial strategy was randomized. The variance of the three measurements was calculated as a measure of reproducibility. The quantity of presented stimuli was recorded as a measure of test time. After the elimination of starting points, absolute scotomata, and series of fields showing a significant trend during the session, 255 measured locations of 27 series were available for evaluation. The mean number of presentations (indicating test time) was 46% (dynamic strategy versus traditional strategy). The variance of the three measurements depended on the sensitivity. In the normal sensitivity range, the dynamic strategy had a markedly lower variance (58%). For relative defects, the variance was higher (141%-156%). According to a benefit/cost calculation, the efficiency of the dynamic strategy was better in all sensitivity ranges and reached a factor of 3 for high sensitivities. The dynamic strategy is considerably more efficient than the traditional strategy using fixed step sizes.

Adult↗
PubMed1995

The effect of a single amino acid substitution within the V3 loop of HIV-1 gp120 on HLA-DR1-restricted CD4 T-cell recognition.

Viral variation has been proposed to play a role in the pathogenesis of human immunodeficiency virus type-1 (HIV-1) infection, and is an important consideration in vaccine design. During the course of an infection, isolates with sequence changes in CD8 T-cell and B-cell epitopes arise. To determine whether sequence variation within the V3 loop of HIV-1 gp120 affects HLA-DR beta 1*0101-restricted CD4 T-cell recognition, we have generated CD4 T-cell clones (TLC) specific to gp120 V3 loop peptides. Four HLA-DR beta 1*0101-restricted groups of TLC were defined by distinct patterns of responses to a panel of peptides, consistent with a highly diverse T-cell repertoire recognizing the 30 amino acid stretch (296-326) of the gp120 V3 loop. Nevertheless, a single residue change at position 311 was found to abolish the recognition of two of the four groups of TLC. This was not due to an effect of the residue at 311 on binding to major histocompatibility complex (MHC), because: (1) irrespective of the residue at 311, peptides competed well with the influenza haemagglutinin peptide 307-319 for binding to cell-bound DR1; and (2) R311-specific TLC were also HLA DR beta 1*0101 restricted. Instead, the substitution of arginine for serine at position 311 blocked the interaction of the peptide with the T-cell receptor. Thus, despite the diversity of the T-cell response to the V3 loop of HIV-1, a single amino acid change can have a considerable influence on the responding T-cell population. As residue 311 is one of the most variable of the V3 loop residues, these results suggest that CD4 recognition can also exert pressure on viral variation consistent with a role for these cells in antiviral immunity.

Amino Acid Sequence↗
PubMed1995

Perineal descent at defecography in women with straining at stool: a lack of specificity or predictive value for future anal incontinence?

OBJECTIVE: To determine (1) whether patients complaining of straining at stool have pelvic floor descent and anal abnormalities similar to those of patients with anal incontinence and (2) whether these patients are prone to develop anal incontinence. METHODS: To answer the first question we used defecography to study perineal floor position at rest, during maximal contraction of the anal sphincter and during straining, and we performed anorectal manometry in 46 women with straining at stool but without anal incontinence at the beginning of the study, and in 46 women with idiopathic anal incontinence, matched for age. To answer the second question, we performed a 5-year follow-up study to determine whether anal incontinence had developed in those women with straining at stool. RESULTS: Perineal floor position at rest, during maximal contraction of the sphincter and during straining, resting pressure in the upper part of the anal canal, maximal amplitude and duration of the voluntary contraction were similar in the 46 women with straining at stool and the 46 women with idiopathic anal incontinence. In the follow-up study, 24 of the 46 women with straining at stool were contacted. The incidence of anal incontinence after 5 years was higher among these 24 women than in a control group of 20 women (13 out of 24 versus three out of 20, for women with straining at stool versus controls respectively; P < 0.01). The 13 patients with straining at stool who became incontinent had, at the initial investigation, a lower maximal amplitude of voluntary contraction, greater perineal descent at rest and less elevation of the pelvic floor during maximal contraction of the anal sphincter than the other women (P < 0.05). CONCLUSION: Women with chronic straining at stool have perineal descent at rest and during straining similar to that of incontinent women. Women with chronic straining are also prone to develop anal incontinence, suggesting that perineal descent at defecography in women with straining at stool may predict future anal incontinence.

Aged↗
PubMed1995

[Echo-planar imaging of the brain].

In this review, the clinical utility of echoplanar techniques in MRI of the brain is discussed. Comparison of high-resolution EPI with SE/turbo-SE shows high image quality of EPI in the supratentorial brain. In the infratentorial region, however, susceptibility artifacts limit image quality. For the assessment of neuronal brain activation utilizing the intrinsic contrast of blood (BOLD), EPI has definite advantages over other techniques of functional MRI. Due to its superior temporal resolution and multislice capabilities, EPI allows for analysis of complex neuronal activation patterns. Diffusion imaging benefits from the lack of bulk motion artifacts and serves primarily to detect early stroke. Three methods of perfusion imaging (rel. blood volume, rel. blood flow) are discussed: the susceptibility artifact method (T2*), the relaxitivity method (T1), and the signal-labelling technique (STAR). Perfusion imaging may have a clinical impact in the assessment of brain tumors and cerebral ischemia.

Artifacts↗
PubMed1994

1H-NMR studies of the natriuretic peptide urodilatin: sequence-specific resonance assignment.

The recently discovered 32 amino-acid natriuretic peptide urodilatin was chemically synthesized and subjected to two-dimensional proton nuclear magnetic resonance (NMR) spectroscopy studies in aqueous solution in order to determine the structural state of urodilatin. In contrast to earlier studies on very closely related peptides, such as cardiodilatin (CDD/ANP-99-126) and brain natriuretic peptide (BNP), spectra of urodilatin were extremely well resolved even in millimolar concentration in H2O so that the complete sequence specific resonance assignments could be achieved. No long range NOEs could be detected, except between residues close to the single cystine bond. This leads to the conclusion that urodilatin in aqueous solution is a random coil peptide with the exception of the region around the cystine bond.

Amino Acid Sequence↗
PubMed1994

Cooperativity and stoichiometry of substrate binding to the catalytic sites of Escherichia coli F1-ATPase. Effects of magnesium, inhibitors, and mutation.

The fluorescence of residue Trp beta 331 in beta Y331W mutant Escherichia coli F1-ATPase was used as reporter probe to investigate the effects of magnesium ions, inhibitors, and mutation on substrate (ATP) binding stoichiometry and cooperativity. It was found that Mg2+ is required for catalytic site binding cooperativity. In the absence of magnesium, ATP bound to three independent catalytic sites, each with Kd = 76 microM. In contrast, MgATP bound to three catalytic sites with Kd1 < 50 nM, Kd2 = 0.5 microM, and Kd3 = 25 microM. There was no significant ATPase activity in the absence of Mg2+. Catalysis is therefore correlated with substrate binding cooperativity and the formation of the high-affinity catalytic site 1. Catalytic site 3 had properties similar to those of the isolated beta-subunit nucleotide-binding site. The inhibitors dicyclohexylcarbodiimide and N-ethylmaleimide (in alpha S373C/beta Y331W mutant F1) gave potent inhibition of multisite ATPase activity without significantly affecting MgATP binding stoichiometry or cooperativity. Therefore each seems to selectively attenuate positive catalytic cooperativity. The same conclusions held for the alpha S373F mutation (in alpha S373F/beta Y331W mutant F1). 7-Chloro-4-nitrobenzo-2-oxa-1,3-diazole, however, reduced the catalytic site MgATP binding stoichiometry from three to two, and appears to inhibit catalysis by sterically blocking catalytic site 3.

Adenosine Triphosphate↗
PubMed1994

Tryptophan fluorescence provides a direct probe of nucleotide binding in the noncatalytic sites of Escherichia coli F1-ATPase.

Tryptophan fluorescence was investigated as a tool to study the noncatalytic nucleotide-binding sites of Escherichia coli F1-ATPase. Site-directed mutagenesis, affinity labeling, and lin-benzo-ATP binding studies had shown that residues alpha R365 and beta Y354 are located close to the base moiety of bound nucleotide; here, we mutagenized each to tryptophan. The new tryptophans gave a fluorescence signal indicating an environment of high (alpha W365) or intermediate (beta W354) polarity in unoccupied sites. alpha W365 fluorescence was completely quenched by binding of ATP or ADP, providing a direct, specific probe of noncatalytic site nucleotide occupancy. Using this signal, we measured binding parameters for ATP and ADP, showed that nucleotide binding was magnesium-dependent, and showed that GTP and ITP did bind to some extent, but AMP, GDP, and IDP did not. It was possible to follow initial rates of MgATP hydrolysis and noncatalytic site binding under identical conditions; the results indicated that occupancy of noncatalytic sites was not required for catalysis. Fluorescence from beta W354 was quenched completely by lin-benzo-ATP, but only slightly by ATP or ADP. Probably, residue beta 354 is not as closely juxtaposed to the adenine ring of bound ATP and ADP as is residue alpha 365. With either alpha W365 or beta W354 as donor and catalytic site-bound lin-benzo-ADP as acceptor, no fluorescence resonance energy transfer was detected, indicating that the distance between non-catalytic and catalytic sites is > or = 27 A.

Amino Acid Sequence↗
PubMed1994

Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2'-deoxycytidine.

MAGE-1 is a gene that encodes an antigen on a melanoma cell line that is recognized by cytolytic T-cells. We have used a reverse transcription-polymerase chain reaction assay to analyze expression of the MAGE-1 gene by cell lines from different types of tumors, melanomas from different stages of disease progression, normal diploid cell lines, and melanocyte and nevus tissue from which malignant melanomas are derived. MAGE-1 is expressed by melanoma tissue from all stages of disease, but not melanocytes, nevus tissue, or any normal diploid cell line tested. A fraction of tumor lines derived from various epithelial and neuroectodermal malignancies expressed MAGE-1 but not peripheral blood cells from patients with melanoma. 5-Aza-2'-deoxycytidine (DAC), a demethylating agent, was capable of inducing MAGE-1 expression by a MAGE-1-negative melanoma cell line 888-mel as well as by a number of other melanoma cell lines. At an optimum concentration of 1 microM DAC, MAGE-1 expression was detectable by 24 h, plateaued by 72 h, but remained high for two weeks after removal of DAC from treated 888-mel cells, consistent with induction by demethylation. With the exception of tumor-infiltrating leukocytes, no normal diploid cell line could be induced with DAC to upregulate MAGE-1 expression. DAC-treated 888-mel cells were lysed by a MAGE-1-specific major histocompatibility complex restricted cytolytic T-cell clone, whereas control untreated cells were not, suggesting that production of the antigen encoded by the MAGE-1 gene was induced by DAC and that it was presented in association with major histocompatibility complex class I molecules at the cell surface for T-cell recognition.

Antigens, Neoplasm↗
PubMed1994

Phase I trial of recombinant human macrophage colony-stimulating factor administered by continuous intravenous infusion in patients with metastatic cancer.

BACKGROUND: Macrophage colony-stimulating factor is a bone marrow-derived glycoprotein that can stimulate monocytes and macrophages, resulting in production of factors involved in immune response. In vitro and in vivo preclinical studies in animals have demonstrated that recombinant human macrophage colony-stimulating factor (rHuM-CSF) can have antitumor activity. PURPOSE: A phase I clinical trial was undertaken to evaluate the toxicity, pharmacokinetics, and immunologic effects of rHuM-CSF given by continuous intravenous infusion in patients with cancer. METHODS: Eighteen patients with metastatic solid tumors refractory to conventional therapy were treated with rHuM-CSF. Twelve patients received two 14-day cycles of rHuM-CSF by continuous infusion, with a 2-week interval. Dose escalation levels were 50, 100, and 150 micrograms/kg over 24 hours. Consecutive cohorts of three to six patients were planned at each dose level. Six patients received a modified regimen of four 7-day periods of infusion at 100 micrograms/kg over 24 hours, with 1-week intervals. RESULTS: Dose-limiting toxicity was grade 4 thrombocytopenia at a dose of 150 micrograms/kg over 24 hours in two patients receiving the 2-week regimen. Platelet count nadirs and concomitant monocytosis were seen on days 7-9, but recovery occurred during the treatment period. Macrophage colony-stimulating factor serum levels were maximal on day 1 and returned to near baseline on day 7 of infusion. Patients treated with four 7-day infusions had no treatment-limiting thrombocytopenia. There were no cumulative effects on platelet or monocyte counts or significant constitutional symptoms. Subclinical conjunctival injection was noted in five of 10 patients receiving screening ophthalmologic evaluation. Grade 2 episcleritis was diagnosed in one patient, and asymptomatic perilimbal and retinal hemorrhages were seen in two. Two patients developed sepsis caused by the intravenous line, which required cessation of therapy. No objective responses were documented. CONCLUSION: The maximum tolerated dose of rHuM-CSF given by continuous intravenous infusion for 14 days was 100 micrograms/kg over 24 hours, with rapidly reversible, dose-limiting thrombocytopenia at 150 micrograms/kg over 24 hours. A regimen alternating weekly cycles of infusion avoids dose-limiting toxicity and allows long-term treatment. IMPLICATIONS: The regimen of repeated 7-day infusions may be useful for future studies evaluating rHuM-CSF-activated monocytes in therapy for long-term infectious diseases or in investigation of new modes of cancer therapy using rHuM-CSF in conjunction with a tumor-specific antibody.

Adult↗
PubMed1994

Tryptophan-free Escherichia coli F1-ATPase.

We have engineered a mutant form of Escherichia coli F1-ATPase which is tryptophan-free and contains five mutations, namely delta W28L/alpha W513F/gamma W108Y/gamma W206Y/beta W107F. A strain carrying all five mutations grew normally by oxidative phosphorylation. Purified mutant F1-ATPase showed Vmax and Km both 65% higher than wild-type, resulting in kcat/Km the same as wild-type. The pH dependence of ATPase activity in mutant enzyme was very similar to that in wild-type. Catalytic-site nucleotide-binding characteristics were measured using the analog lin-benzo-ADP and sensitivity to inhibitors was tested using dicyclohexylcarbodiimide, azide and aurovertin. The mutant enzyme was very similar to wild-type in each of these characteristics. The fluorescence spectrum of mutant enzyme confirmed the absence of tryptophan. We have therefore established that it is possible to generate a tryptophan-free enzyme which retains normal catalytic function, oligomeric stability and in vivo assembly.

Adenosine Diphosphate↗
PubMed1994

Myotonic dystrophy and limb girdle muscular dystrophy in one family.

A family is reported in which a 29-year-old woman showed the clinical features of myotonic dystrophy while her 26-year-old brother presented with the clinical picture of limb girdle syndrome. In the affected female, direct genetic testing for the specific myotonic dystrophy mutation on chromosome 19 revealed abnormal expansion of a repeat unit containing the three nucleotides cytosine, thymine, and guanine (CTG)-typical for myotonic dystrophy-while her diseased brother displayed two normal alleles. This supports the hypothesis of the extremely rare occurrence of two clinically and genetically different myopathies in one family. Genetic analysis of six other family members showed that the father of the diseased siblings as well as all of his three brothers and sisters had a pathological CTG repeat expansion, and that the other two family members tested had a normal allelic pattern. The number of CTG repeats in the diseased women was approximately tenfold higher than in her asymptomatic relatives who revealed an abnormal allelic pattern. The increase in CTG repeats with transmission to a subsequent generation in this family was paralleled by a dramatic increase in the severity of myotonic dystrophy.

Adult↗
PubMed1994

Laser Doppler flowmetry of focal ischaemia and reperfusion in deep brain structures in rats.

Monitoring cerebral blood flow during focal ischaemia and reperfusion with established techniques such as hydrogen clearance and autoradiography is difficult. Laser Doppler flowmetry is a new technique, it allows one to continuously measure blood flow in small tissue samples. The objective of this study was to compare laser Doppler flowmetry with hydrogen clearance using a new single fiber probe to obtain measurements in deep brain structures and then to show the temporal profile of cerebral blood flow during focal ischaemia and after reperfusion. First, the single fiber laser Doppler method was compared with the hydrogen clearance method in ten Wistar rats. Second, focal cerebral ischaemia was induced in fifteen Wistar rats using a model of middle cerebral artery occlusion based on the intravascular insertion of a nylon suture; reperfusion occurred after withdrawal of the suture. The laser Doppler probe was placed in the lateral caudatoputamen, and local cerebral blood flow was measured continuously before and during occlusion as well as after reperfusion. The relative blood flow values obtained by the laser Doppler method and the hydrogen clearance method showed a good correlation (r = 0.76) and a linear relationship. A rapid decrease in laser Doppler flowmetry to 42 +/- 16% of former baseline values was seen with occlusion of the middle cerebral artery; during occlusion cerebral blood flow remained at this level. Reperfusion resulted in a heterogeneous pattern of cerebral blood flow as laser Doppler flowmetry values ranged from 25% to 134% of baseline values. The effects of middle cerebral artery occlusion and reperfusion on cerebral blood flow can be monitored on-line with laser Doppler flowmetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Control of methicillin-resistant Staphylococcus aureus in a pediatric burn unit.

BACKGROUND: Control of methicillin-resistant Staphylococcus aureus (MRSA) is particularly difficult in burn units, which are often cited as sources of hospital-wide MRSA outbreaks. We developed a successful MRSA control program and document here its apparent effectiveness in controlling MRSA transmission in a pediatric burn unit. METHODS: An MRSA control program that included surveillance culturing, clinician feedback, flexible, site-specific isolation, and a list of known carriers was consistently applied in a pediatric burn unit through a 7-year period. Microbiology reports of MRSA isolates from patients and environmental surfaces and records of all patients from whom MRSA was isolated were reviewed. RESULTS: During calendar years 1985 through 1991, a total of 991 acutely burned children were admitted to the Boston unit of the Shriners Burns Institute. Forty MRSA cases (4%) were identified. One patient both had MRSA at admission and met our criteria for nosocomial MRSA. Of the remaining 39 patients, 11 had MRSA at admission and 28 had nosocomial MRSA. There were 17 wound infections, two cases of pneumonia, and two bloodstream infections. No deaths were attributed to MRSA sepsis. CONCLUSION: An MRSA control program including surveillance culturing, clinician feedback, flexible, site-specific isolation, and a list of known carriers is associated with a low rate of nosocomial MRSA in a pediatric burn unit.

Adolescent↗